This invention is concerned with an anti-bacterial oral composition containing a bis-biguanido hexane compound such as chlorhexidine and derivative compounds thereof which markedly enhances the activity of the bis-biguanido hexane compound.
Bis-biguanido hexane compounds such as chlorhexidine and its salts are well known in the art for their anti-bacterial activity and have been used in aqueous-based oral compositions to counter dental plaque and caries formation by bacteria in the oral cavity. Chlorhexidine is active against a wide range of gram-positive and gram-negative organisms, yeast, fungi, facultative anaerobes and aerobes.
Chlorhexidine is a strong base and is most stable in the form of its salts. The most common derivative is the digluconate salt because of its high water-solubility. Chlorhexidine, however, is a very reactive compound and hence its combination with other constituents in oral compositions often results in salt-formation, precipitation and other undesirable effects which reduce its activity or the commercial acceptability of the composition. Oral preparations such as mouthrinses contain water-alcohol mixtures as the oral vehicle, colorants, natural and artificial sweeteners, flavorants, buffers, surfactants and other additives. Many of these preparations have been demonstrated to be unacceptable because one or more of the additives therein either react with chlorhexidine, reduce its activity or form other undesirable products. For example, saccharin forms salts with chlorhexidine and reduces it's activity; buffers such as citrates and phosphates form insoluble salts with chlorhexidine; acesulfame K causes precipitation of chlorhexidine in the oral vehicle; and flavorants such as cinnamic aldehyde react with the amino groups of chlorhexidine to form Schiff bases. Solvents such as polyethylene glycol also inactivate chlorhexidine.
Surfactants have also been employed in oral preparations containing chlorhexidine primarily to solubilize the lipophilic flavorants contained therein. Without a surfactant an opaque formulation results rendering the preparation commercially unacceptable. However, many surfactants deactivate chlorhexidine and are therefore unsuitable.
In Japanese Application No. 57-212005, published June 12, 1984, a composition for oral use is provided including a bis-biguanido hexane such as chlorhexidine and a non-ionic surfactant which prevents the deactivation of chlorhexidine by the surfactant. This prevention is accomplished by the addition to the composition of a higher alcohol such as a fatty acid alcohol having from 10 to 20 carbon atoms. Such alcohols include lauryl alcohol, myristyl alcohol, cetyl alcohol and stearyl alcohol which are used in amounts ranging from 0.1% to 10% by weight of the composition. The non-ionic surfactants include saccharides such as sucrose, maltose, maltitol and lactitol or a free fatty acid ester of a saccharide alcohol such as sucrose fatty acid ester. The compositions may also include minor amounts of other ingredients such as phosphate buffers, cellulose derivatives, flavorants, enzymes, fluorides, and sorbitol.
The present invention, however, provides an oral preparation containing chlorhexidine and derivative compounds in combination with certain selected non-ionic surfactants and sorbitol in relatively high concentrations which increases the bioavailability or activity of the chlorhexidine without the necessity or desirability of higher alcohol additions.